Author: Isabelle Audo (France)
Co-authors: Jose Alain Sahel, Pierre Olivier Barale, Saddek Mohand Said, Celine Devisme, Chloe Pagot, Perrine Chapon
Purpose
RPE65-related IRD is a rare condition caused by biallelic mutations in RPE65. Loss of RPE65 function causes photoreceptor dysfunction and degeneration, leading to blindness. The launch of voretigene neparvovec, a gene therapy product indicated for treatment of patients with sufficient viable retinal cells and confirmed biallelic RPE65 mutations constitute a first gene therapy success for IRD. The CHNO was the first European center to use voretigene neparvovec and has so far one of the largest and longest follow-up in an European cohort of treated patients. It has significant experience with treatment administration and follow-up in real-life conditions. In the development program of voretigene neparvovec, efficacy was measured by the Multi-Luminance Mobility Test, specifically-developed for IRD-patients. This test requires patients to follow a maze and avoid obstacles, under different light levels. As it is difficult to implement, it is not usually used in routine follow-up and centers rely on usual assessments. The CHNO has access to a similar maze platform called Streetlab® which can test functional vision through mobility testing, and is able to use it in routine follow-up. The study’s purpose was to report one-year effectiveness and safety outcomes of voretigene neparvovec treatment including functional vision with the Streetlab® platform.
Setting/Venue
This is a descriptive, non-interventional study with secondary use of data of patients with inherited retinal dystrophy associated with biallelic mutations in RPE65, treated with voretigene neparvovec subretinal gene therapy at CHNO des Quinze-Vingts between December 2018 and November 2019 and with at least a 1-year follow-up period who did not object to the secondary use of their data. Data were collected from patients’ medical records.
Methods
Voretigene neparvovec is a one-time treatment, administered at a dose of 1.5 x 1011 vector genomes to each eye, delivered in a total subretinal volume of 0.3 ml. The individual administration procedure to each eye was performed on separate days, no fewer than 6 days apart. Baseline visit was defined as the last visit before the surgery. Patient’s follow-up visits in routine practice usually take place at 1, 3, 6 and 12 months after the surgery of the second eye. The data collected aimed to evaluate efficacy, safety and to describe the surgical procedure. Efficacy was assessed by both visual function and functional vision assessments. Visual function was assessed using visual acuity of each eye, full-field stimulus threshold (FST) of each eye and monocular and binocular kinetic visual field. Functional vision was assessed using the Streetlab® system. It was designed to evaluate the evolution of mobility following treatment. The courses were set up to represent a daily life street and included elements of varying contrast and volume. Patients were instructed to follow the path under four lighting conditions (2, 7.5, 50 and 500 lux), while avoiding touching obstacles and walls.
Results
Due to the recent implementation of the LIGHT study, a full and complete analysis of the data, while pending, is not yet available at this time. Nevertheless, our preliminary results were promising as all 12 patients reported having improved vision in dimly lit environment. Analysis are being finalized and will be shared during at the congress.
Conlusions
This study is the first study to generate real-world data using such a large cohort of patients with a one-year period follow-up. The addition by the CHNO of a mobility test to assess the evolution of functional vision in their routine follow-up protocol in addition to the FST allows this study to give further insights on the efficacy of voretigene neparvovec treatment during the first year post-surgery.
Financial Disclosure
RESEARCH COLLABORATION FUNDED BY NOVARTIS
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